POS0957 EXTERNAL VALIDATION OF THE ALTERNATIVE ANKYLOSING SPONDYLITIS DISEASE ACTIVITY SCORE IN THREE PHASE-3 RCTs
Authors: A. Ortolan, S. Ramiro, D. Van der Heijde
Journal: Annals of the Rheumatic Diseases (2022)

Background In axial spondyloarthritis (axSpA), an alternative ASDAS (altASDAS) was developed to be used when Patient Global Assessment (PGA) is unavailable. AltASDAS replaces PGA with BASDAI total score and has so far only been internally validated [1]. Objectives To test the psychometric properties of altASDAS in an external cohort, according to the OMERACT filter 2.0 (truth, discrimination; feasibility was evaluated in our previous work). Methods Cohorts from the COAST trial programme of ixekizumab (COAST-V,-W,-X;primary endpoint: 16-week), enrolling radiographic/non-radiographic axSpA (r-/nr-axSpA) patients, were pooled. AltASDAS was calculated for all evaluations. Truth was assessed by: 1) agreement with original-ASDAS, as a continuous score and as a categorical variable (disease activity-DA-states), with intraclass correlation coefficients (ICC) and weighted Kappa respectively; 2) Bland &amp; Altman plots with mean difference (MD) and 95% limits of agreement (LoA) 3) comparison of Pearson correlations of altASDAS and original-ASDAS with other constructs. Discrimination was tested by 1) the ability of altASDAS to distinguish high/low DA states according to an external anchor (nocturnal pain&gt;6 indicating high DA) 2) agreement (kappa) with original-ASDAS in major/clinically important-improvement (MI/CII) achievement at 16-weeks 3) comparison of number of patients reaching MI/CII in the treatment versus placebo arm at 16-weeks, according to original and altASDAS (higher Chi-square=better discrimination). Results 958 patients were included, 70% males, mean age 42.7 years, 68% r-axSpA. Truth: 1) agreement with original-ASDAS: ICC=0.97 (95%CI:0.93-0.99), kappa=0.84 (0.83-0.85) 2) MD with original-ASDAS: 0.14; 95% LoA -0.56 to 0.28 3) correlation coefficients of altASDAS with related constructs were within a pre-specified 0.3-wide band around those between original-ASDAS and the same construct (Table 1 a ). Discrimination altASDAS discriminated between DA states (Table 1 b ) and in sensitivity to change (Kappa with original-ASDAS for MI=0.87 95%CI:0.83-0.91; for CII=0.93; 95%CI:0.90-0.95) and Table 1 e c Table 1. Psychometric properties of alternative Ankylosing Spondylitis Disease Activity Score (altASDAS) a) Truth: correlations with constructs related to disease activity Data expressed as correlation coefficient r Function (BASFI ) Quality of Life (MCS ) Quality of life (PCS ) Overall functioning and health (ASAS HI ) Original-ASDAS 0.58 -0.11 -0.48 0.35 altASDAS 0.57 -0.11 -0.47 0.35 b) Discrimination: disease activity states Anchor to define disease activity: Nocturnal pain (NRS 0-10) NRS &gt;6 Mean ASDAS (SD ) NRS ≤ 6 Mean ASDAS (SD ) SMD Original-ASDAS 3.99 (0.76) 2.61 (0.86) -1.68 altASDAS 3.87 (0.83) 2.46 (0.96) -1.57 c) Discrimination: sensitivity to change Treatment N (% ) Placebo N (% ) Chi-square N° of patients 628 272 - Original-ASDAS MI 151 (24) 12 (4) 49.3 altASDAS-MI 167 (26) 13 (5) 56.4 Original-ASDAS CII 342 (54) 62 (23) 76.9 altASDAS-CII 350 (56) 64 (23) 79.2 BASFI: Bath Ankylosing Spondylitis Functional Index, MCS and PCS: mental and physical component summary of Short-Form 36; ASAS HI: ASAS Health Index; NRS: Numerical rating scale; SD: standard deviation; SMD: standardised mean differences; MI and CII: Major and Clinically Important Improvement Conclusion AltASDAS was shown to be truthful and discriminative in an external cohort and as such has been fully validated and can be used in cases when PGA is unavailable. References [1]Ortolan A et al. Rheumatology (Oxford). 2021;60:638-48. Acknowledgements The authors wish to thank Lilly for providing data of the trials COAST-V, ( NCT02696785 ), COAST-W ( NCT02696798 ) and COAST-X ( NCT02757352 ). Disclosure of Interests Augusta Ortolan Grant/research support from: 2020 New Horizon Fellowship, Sofia Ramiro Consultant of: Consultancy/speaking fees from AbbVie, Eli Lilly, MSD, Novartis, UCB, Sanofi, Grant/research support from: Research grant from MSD, Désirée van der Heijde Consultant of: Consulting fees AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB, Employee of: Pharma Director of Imaging Rheumatology bv